Oral Presentation Society for Molecular Biology and Evolution Conference 2016

Revisiting an old evolutionary question: did the S mutation of the β-globin gene result from a single or multiple mutations? (#123)

Sandra Oliveira 1 2 , Giovanni Destro-Bisol 3 4 , António M. Santos 1 2 , Jorge Rocha 1 2
  1. CIBIO, Vairão, VILA DO CONDE, Portugal
  2. Faculdade de Ciências da Universidade do Porto, Porto, Portugal
  3. Dipartimento di Biologia Ambientale, Sapienza Università di Roma, Rome, Italy
  4. Istituto Italiano di Antropologia, Rome, Italy

The S mutation of the β-globin gene (HBB*S) in humans is a well-studied example of an advantageous allele with a protective role against malaria in the heterozygous carrier state. More than 50 years ago, Livingstone proposed that the emergence of tropical agriculture provided ideal habitats for the spread of malaria-transmitting mosquitoes allowing the rapid diffusion of a single, relatively recent HBB*S mutation. However, the concept of a single mutation was challenged by the finding that different HBB*S-linked haplotypes predominated in various non-overlapping geographical regions of Africa, India and the Arabian Peninsula. Currently, the most favored hypothesis explaining the geographic segregation of HBB*S-linked haplotypes is that HBB*S variants originated independently by recurrent mutation in each region where a single haplotype predominates. However, little work has been done to explicitly examine the effects of the spatial diffusion of the HBB*S allele on linked haplotype variation. Here, we explored a computer simulation framework to assess the evolution of HBB*S-linked haplotype variation in time and space, using a stepping stone model for the dispersal of an advantageous allele under different demographic scenarios. Moreover, we compared the simulated scenarios with an empirical dataset, consisting of 330 high resolution HBB*S-linked haplotypes defined by 11 microsatellites distributed across a 525 kb region. We show that the wave of advance of the HBB*S allele can originate patterns that mimic the spatial distribution of S-haplotypes, by creating several patches (or sectors), each formed by contiguous populations that share unique S-linked modal haplotypes exhibiting levels of haplotype diversity that are compatible with those currently observed in Africa. These findings bring back the hypothesis of a single origin as a plausible explanation for the evolution of the S mutation.